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Identification and management of GCK-MODY complicating pregnancy in Chinese patients with gestational diabetes.

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机构: [1]Shanghai Diabetes Institute, Department of Endocrinology & Metabolism, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. [2]Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600 Yishan Road, Shanghai, 200233, China. [3]The Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China. [4]Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China. [5]Department of Endocrinology, Weihai Municipal Hospital, No. 70, Heping Road, Weihai, 264200, China. [6]School of Population Health and Environmental Science, King's College London, London, UK. [7]Department of Pediatrics, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA. [8]School of Medicine, Huanghuai University, Zhumadian, 463000, Henan, China. [9]Department of Endocrinology, School of Medicine, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University, Shanghai, China. [10]Department of Endocrinology, The first affiliated hospital of Wenzhou Medical University, The South of Shangcai Village, Nanbaixiang Town, Ouhai District, Wenzhou, 325000, Zhejiang, China. [11]Department of Endocrinology, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, China. [12]Department of Nutritional Sciences and Toxicology, University of California at Berkeley, Berkeley, USA. [13]Department of Endocrinology & Metabolism, Putuo Hospital Attached to Shanghai University of Traditional Chinese Medicine, 164 Lanxi Road, Shanghai, 200000, China. [14]Department of Nephrology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China. [15]Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. [16]State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai, 200240, China. [17]Department of Internal Medicine, Charles R. Drew University, Los Angeles, USA. [18]David Geffen School of Medicine at University of California, Los Angeles, USA
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关键词: GCK-MODY complicating pregnancy ・ Gestational diabetes mellitus (GDM) ・ Identification ・ Management ・Pregnancy outcome

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Precise differentiation of glucokinase (GCK) monogenic diabetes from gestational diabetes mellitus (GDM) is critical for accurate management of the pregnancy outcome. We screened GCK-MODY complicating pregnancies in Chinese GDM patients, explored the pathogenesis of novel GCK mutations, and evaluated the patients' pregnancy outcome and management. The GCK gene from 411 GDM patients was screened with PCR-direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and 15 GCK mutations were identified. We also retrospectively analyzed a total of 65 pregnancies from 21 GCK-MODY families, wherein 41 were from 15 maternal families and 24 were from six paternal families. Bioinformatic analysis and biochemical functional study were conducted to identify novel GCK mutations. In total, we identified 21 GCK mutations: 15 from the 411 GDM patients and six from 24 fathers. Of th Asp78Asn (GAC → AAC), Met87Arg (ATG → AGG), Leu451Val (CTT → GTT), Leu451Pro (CTG → CCG) and 1019 + 20G > A e mutations, five, i.e., were novel and deleterious, with markedly decreased enzyme activity and thermal stability. The unaffected offspring of GCK mutation-affected mothers were heavier than affected offspring (p < 0.001). Of 21 insulin-treated affected mothers, 10 had maternal hypoglycemia (47.6%) and seven had perinatal complications (33.3%), and the affected offspring of the insulin-treated affected mothers had significantly lower birth weights than that of the 20 diet-control affected mothers (p = 0.031). In this study, the prevalence of GCK-MODY complicating pregnancy in Chinese GDM patients was 3.6% (15/411). The defective GCK may contribute to the hyperglycemia in GCK-MODY. Insulin therapy is not beneficial for GCK-MODY complicating pregnancy and therefore should not be recommended.© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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大类 | 3 区 生物学
小类 | 4 区 细胞生物学
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大类 | 3 区 生物学
小类 | 3 区 细胞生物学
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Q3 CELL BIOLOGY
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Q3 CELL BIOLOGY

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第一作者机构: [1]Shanghai Diabetes Institute, Department of Endocrinology & Metabolism, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiaotong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
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